Catalytic asymmetric synthesis reaction using an optically active catalyst (referred to as an “asymmetric catalyst” hereinafter) is capable of synthesizing a large amount of an optically active compound using a very small amount of an asymmetric catalyst, and is thus highly valued in industrial use. In particular, a synthesis method referred to as “asymmetric reduction” has the advantage of high reaction efficiency and the advantage that by-products such as an inorganic salt and the like are not produced in use of hydrogen gas as a raw material. Therefore, this synthesis method is economical and harmonizes with environments.
The catalytic asymmetric synthesis reaction is aimed at producing a product with high optical purity, the optical purity depending on the performance of the asymmetric catalyst used in the reaction. Although a transition metal complex is generally used as the asymmetric catalyst, the optical purity of a reaction product is mostly determined by the type of the asymmetric space created by the ligand coordinating to a transition metal of the complex at a reaction site. Therefore, in development of an asymmetric catalyst, it is most important to design the configuration of a ligand so as to realize excellent catalytic activity and stereoselectivity.
In recent years, asymmetric ligands have been actively studied, and various asymmetric ligands have been developed. In particular, phosphine ligands play an important role in catalytic asymmetric synthesis reaction using a transition metal complex. A huge amount of ligands has been designed and synthesized so far.
The inventors of the present invention proposed 1,2-bis (alkylmethylphosphino)ethane capable of efficiently asymmetrically hydrogenating various α,β-unsaturated α-amino acids and esters thereof, having a phosphorus-chiral trialkyl group, and represented by the following formula (9):
(wherein R represents cyclopentyl, cyclohexyl, tert-butyl, 1,1-diethylpropyl, or 1-adamantyl) (Non-patent Document 1).
Among ligands having phosphorus-containing heterocyclic rings, ligands having strong structures due to heterocyclic rings are known to suppress the number of conformations of a chelate formed by coordination to a central metal and create a stable asymmetric space (Non-patent Document 2).
An optically active phosphorus-chiral diphosphine represented by formula (9) has no heterocyclic ring, and it is thus difficult to say, depending on the substituent represented by R and bonded to each phosphorus atom, that the structure of the ligand is stable.
[Non-patent Document 1]
J. Am. Chem. Soc., 1998, 120, pp. 1635-1636
[Non-patent Document 2]
J. Am. Chem. Soc., 1993, 115, pp. 10125-10138
Accordingly, an object of the present invention is to provide a process for producing a novel optically active phosphorus heterocyclic dimer useful as a ligand of a transition metal catalyst which is used for catalytic asymmetric synthesis such as asymmetric hydrogenation reaction and the like, the ligand capable of creating a stable asymmetric space when coordinating to a central metal.